Focal articular defects are one of the most common types of articular lesions and are associated with progressive degeneration of articular cartilage in both osteoarthritic and asymptomatic knees. Prior investigations on the mechanics of focal articular defects and on cartilage mechanobiology suggest that the presence of a focal defect causes mechanical overload of the adjacent and opposing articular cartilage, and that this overload has direct consequences for the viability, mechanical competence, and mechano- responsiveness of the adjacent and opposing cartilage. Study of the mechanical environment of focal defects may therefore elucidate the biological and biomechanical mechanisms by which these defects can lead to larger scale cartilage loss and compromised joint function. However, little quantitative information is available on the intra-tissue strains, stresses, pressures, and fluid velocities in the vicinity of articular defects. This fellowship application proposes a set of initial studies that will characterize the mechanical environment of focal articular defects. These studies are the central component of the research training plan that will broaden the PI's background in the mechanobiology of skeletal healing and facilitate the PI's transition into the research area of articular cartilage defect repair. The hypothesis of the proposed work is that for physiologic joint loading, the local mechanical environment of a focal articular defect differs from that of the intact articular layer;moreover, the mechanical environment of the defect can be controlled through defined alterations in the applied joint motions. Two specific aims are proposed. Aim #1 will apply compression, sliding, and rolling movements to opposing osteochondral slices both before and after creation of a full-thickness, focal defect. The strains induced in the tissue surrounding and opposing the defect site will be measured via digital correlation of images in which the chondrocyte nuclei have been fluorescently stained. Aim #2 will estimate, using specimen-specific finite element (FE) models, the intra-tissue pressures, stresses, and fluid velocities that occur in the cartilage during the experiments in Aim #1. Validation of the FE results will be performed by comparing the FE-computed strain distributions with those measured in Aim #1. The methods and results from these studies will lay the foundation for subsequent biomechanical investigations that seek to define relationships between mechanical factors and further progression of defects, and for subsequent mechanobiological investigations aimed at manipulating the local mechanical environment in order to enhance healing. Taken together, the findings from this work will constitute an important initial milestone for an integrated approach to the biomechanics and mechanobiology of cartilage defects that should lead the way to new treatment approaches in articular cartilage repair. PUBLIC HEALTH RELEVANCE: Injuries to articular cartilage are common and are associated with progressive cartilage degeneration and loss of joint function. Although results of prior studies have suggested that the presence of a defect in articular cartilage leads to accelerated cartilage destruction through mechanical overload of the surrounding tissue, little is known about the mechanical environment of these defects. The proposed research will quantify relationships between this mechanical environment and joint loads/motions, with the long-term goal of developing new treatment approaches in articular cartilage repair.